1. Field of the Invention
The present invention relates to a HSP27 mutation (S135F) mediated Charcot-Marie-Tooth disease animal model.
2. Description of the Related Art
The experiment using an animal model is unavoidable and has to be done before treating human in the study targeting human for the development of a new drug and a novel treatment method. However, considering how big is the number of human diseases, the number of animal models that can copy such human disease is very small, which has been a big barrier for the development of a new drug and a novel technique for disease treatment. A variety of animal models can be constructed with different characteristics and effects according to the purpose of use. The methods to construct disease animal models known so far can be divided into three groups. First, it is the method to use a natural mutant form as an animal disease model; the second is the experimental method to induce disease by administering a chemical or transplanting a manipulated cell line; and the most recent method is the transfection via gene transplantation developed fast from the molecular genetical approach. For the study to develop a new drug and a novel treatment method, it is very important to establish an efficient animal model construction system based on various different approaching methods for securing animal models and co-operation of them.
Hereditary peripheral neuropathy is largely divided into three categories: which are hereditary motor and sensory neuropathy (HMSN), hereditary motor neuropathy (HMN), and hereditary sensory neuropathy (HSN). Among them, hereditary motor and sensory neuropathy occupies the majority of the patients and is also well known as Charcot-Marie-Tooth disease (CMT). Charcot-Marie-Tooth disease was first identified by French scientists Charcot and Marie and English Tooth in 1886. Since then, the disease has been called as CMT after the first letters of their names. Charcot-Marie-Tooth disease is the general name for all the genetic disease with defect in motor neurons and sensory neurons, and has the highest incidence rate (1/2500 people) among rare diseases. In the past, this disease was understood rather simply as the disease caused by muscle atrophy in the distal lower leg. Patients with this disease have legs in the shape of a champagne bottle standing up side down because of the muscle atrophy. However, this disease is now recognized as a syndrome rather than a single disease. There has been new additions recently to CMT pathogenesis, which is a big help not only for the pathophysiological study but also for the classification of complicated clinical types and genotypes.
Over the past research years, at least 40 genetic loci for hereditary motor and sensory neuropathy have been identified by gene cloning technique and at least 20 causing genes have also been identified. However, many of hereditary motor and sensory neuropathy patients have still be confirmed not to be associated with the above identified loci, suggesting that there would be at least 50 more causing genes of HMSN. So, the constituents that form various different nervous tissues have been identified. Likewise, it is expected that there might be a variety of types of hereditary neuropathies as there are a variety of hereditary muscular dystrophies. As a potential reasonable drug therapy for CMT1A, the most frequent type of HMSN, onapriston, ascorbic acid, and NT-3 (neurotrophin-3) have been drawing our attention in relation to diagnosis and treatment as well.
Heat shock protein (HSP) is well known as molecular chaperone and anti-apoptotic protein, which is expressed in most cells and well preserved therein. Heat shock proteins are divided into five groups according to the amino acid sequence and molecular weight, which are 100˜110 kDa family, 83˜90 kDa family, 66˜78 kDa family, 60 kDa family, and 15˜30 kDa family. HSP27 belongs to the small heat shock protein family and is expressed in mammal tissues including muscle and nervous tissue. HSP27 is widely distributed in motor neurons and sensory neurons.
HSP27 is the low molecular protein that is functioning in many ways in cells. This protein forms a colony itself for self-defense against external environmental stimuli such as free radicals or toxins.